First Drug Targeting HER2-Mutant Non-Small Cell Lung Cancer Approved by FDA

Memorial Sloan Kettering Cancer Center, August 12 2022

The U.S. Food and Drug Administration (FDA) recently sanctioned the use of trastuzumab deruxtecan, also known as T-DXd or Enhertu®, for treating advanced non-small cell lung cancer (NSCLC) marked by mutant HER2. This drug, previously employed for HER2-positive breast cancer, has now garnered approval for NSCLC with mutant HER2. Memorial Sloan Kettering Cancer Center’s (MSK) study on trastuzumab deruxtecan, conducted by researchers and led by Bob Li, emphasized the benefits of the drug in combating HER2-mutant NSCLC. The promising results of the research were presented at the European Society for Medical Oncology (ESMO) Congress 2021 and were later published in The New England Journal of Medicine (NEJM).

Traditionally, treating HER2-mutant NSCLC has been challenging, with previous approaches yielding inconsistent outcomes. Approximately 3% of nonsquamous NSCLC cases are fueled by HER2 genetic mutations, affecting patients who are typically younger, female, never-smokers, and prone to poor prognoses and brain metastases. While HER2 gene targeting has revolutionized cancer treatment in breast and gastric cancers, no HER2-targeted therapies were approved for NSCLC until trastuzumab deruxtecan. The phase 2 DESTINY-Lung01 trial, involving 91 patients across North America, Europe, and Asia, showed promising results with 54.9% of patients

experiencing a confirmed objective response and almost all patients displaying disease control and tumor size reduction. Notably, trastuzumab deruxtecan is the first antibody-drug conjugate utilized for lung cancer, the primary therapy targeting HER2 mutations in lung cancer, and the first HER2-targeted treatment for lung cancer to receive a Breakthrough Therapy designation from the FDA, earning accelerated approval.

In conclusion, the approval of trastuzumab deruxtecan marks a significant advancement in precision medicine for NSCLC, especially for patients with HER2-mutant tumors. The success of this drug signifies a breakthrough in the treatment landscape for a subset of NSCLC patients who previously had limited therapeutic options. The study’s outcomes bring hope for improved outcomes and better quality of life for individuals grappling with HER2-mutant NSCLC, demonstrating the valuable contributions of MSK’s research and the potential for personalized treatment strategies in oncology.

To read the full article, visit the Memorial Sloan Kettering Cancer Center website.